Modeling HIV-1 Intracellular Replication

Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular replication where infected cells undergo a single cycle of virus replication. A cell is modeled as an individual entity with certain states and properties. The model is stochastic and keeps track of the main viral proteins and genetic materials inside the cell. Two simulation approaches are used for implementing the model: rate-based and diffusion-based approaches. The results of the simulation are discussed based on the number of integrated viral cDNA and the number of viral mRNA transcribed after a single round of replication. The model is validated by comparing simulation results with available experimental data. Simulation results give insights about the details of HIV replication dynamics inside the cell at the protein level. Therefore the model can be used for future studies of HIV intracellular replication in vivo and drug treatment.

[1]  Peter M. A. Sloot,et al.  A complex automata model of HIV-1 co-receptor tropism: Understanding mutation rate pressure , 2007 .

[2]  P ? ? ? ? ? ? ? % ? ? ? ? , 1991 .

[3]  A. Perelson,et al.  Dynamics of HIV infection of CD4+ T cells. , 1993, Mathematical biosciences.

[4]  Christian Jacob,et al.  Immunity Through Swarms: Agent-Based Simulations of the Human Immune System , 2004, ICARIS.

[5]  Marian Bubak,et al.  From molecule to man: Decision support in individualized E-health , 2006, Computer.

[6]  L. You,et al.  Stochastic vs. deterministic modeling of intracellular viral kinetics. , 2002, Journal of theoretical biology.

[7]  Salim Khan,et al.  A multi-agent system for the quantitative simulation of biological networks , 2003, AAMAS '03.

[8]  S. Shorte,et al.  Quantitative four-dimensional tracking of cytoplasmic and nuclear HIV-1 complexes , 2006, Nature Methods.

[9]  J. Rossi,et al.  Progress and prospects: RNA-based therapies for treatment of HIV infection , 2007, Gene Therapy.

[10]  M A Nowak,et al.  A model of lymphocyte recirculation. , 1997, Immunology today.

[11]  F Castiglione,et al.  An enhanced agent based model of the immune system response. , 2006, Cellular immunology.

[12]  Peter M. A. Sloot,et al.  Cellular Automata Model of Drug Therapy for HIV Infection , 2002, ACRI.

[13]  Joc Cing Tay,et al.  Sufficiency verification of HIV-1 pathogenesis based on multi-agent simulation , 2005, GECCO.

[14]  Kenneth Webb,et al.  Cell modeling using agent-based formalisms , 2004, Proceedings of the Third International Joint Conference on Autonomous Agents and Multiagent Systems, 2004. AAMAS 2004..

[15]  Mike Holcombe,et al.  Formal agent-based modelling of intracellular chemical interactions. , 2006, Bio Systems.

[16]  A. Perelson,et al.  A model of HIV-1 pathogenesis that includes an intracellular delay. , 2000, Mathematical biosciences.

[17]  J. Yin,et al.  Quantitative intracellular kinetics of HIV type 1. , 1999, AIDS research and human retroviruses.

[18]  Arancha Casal,et al.  Agent-based modeling of the context dependency in T cell recognition. , 2005, Journal of theoretical biology.

[19]  Lin Shen,et al.  Decay dynamics of HIV-1 depend on the inhibited stages of the viral life cycle , 2008, Proceedings of the National Academy of Sciences.

[20]  L. Karageorgos,et al.  Stepwise analysis of reverse transcription in a cell-to-cell human immunodeficiency virus infection model: kinetics and implications. , 1995, The Journal of general virology.

[21]  P. Barbosa,et al.  Kinetic analysis of HIV-1 early replicative steps in a coculture system. , 1994, AIDS research and human retroviruses.

[22]  P. Sonigo,et al.  Analysis of Early Human Immunodeficiency Virus Type 1 DNA Synthesis by Use of a New Sensitive Assay for Quantifying Integrated Provirus , 2003, Journal of Virology.

[23]  P. Sloot,et al.  Elastic light scattering from nucleated blood cells: rapid numerical analysis. , 1986, Applied optics.

[24]  Frederic D. Bushman,et al.  A quantitative assay for HIV DNA integration in vivo , 2001, Nature Medicine.

[25]  Mark L. Pearson,et al.  Complete nucleotide sequence of the AIDS virus, HTLV-III , 1985, Nature.

[26]  P. Coveney,et al.  HIV decision support: from molecule to man , 2009, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.